To the birthday of professor A. M. Davison, editor emeritus of NDT
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Journal Article↗
Biomedical subjects
T Drueke
Publications and source records attributed to T Drueke.
Professor F. Kokot, katowice, poland
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Journal Article↗
A stable animal model of diet-induced calcium oxalate crystalluria.
Twenty male Wistar rats, weighing 150 g, were placed in metabolic cages on a 30% sucrose diet for 7 days, before allocation to two groups: a control group (n = 5) and a lactose group (n = 15). They received respectively a 30% sucrose diet or a 30% lactose diet for 8 weeks, each containing 0.67% calcium and 0.38% phosphorus. After 4 (T1) and 8 (T2) weeks, the serum calcium (Ca) and citrate levels were significantly (P < 0.01) higher in rats fed the lactose diet. Serum alkaline phosphatase activity was increased in the lactose group (P < 0.01) at T1 and T2. The lactose-rich diet induced an increase in urinary Ca excretion at T1 and T2; citrate excretion was only enhanced at T2 (P < 0.001). No difference between the two groups was observed in urinary oxalate (Ox) excretion or creatinine clearance. Crystalluria analysis revealed a marked number (>300/mm3 at T1 and T2) of calcium oxalate dihydrate crystals (COD) in rats fed the lactose-rich diet, whereas no COD crystals were observed in sucrose-fed control rats at any time point. The formation of COD crystals in lactose-fed rats was related to an increase in calcium oxalate (CaOx) product (pCaOx), which was respectively 12.6 vs 3.9 at T1 and 10.5 vs 1.8 at T2, and an increase in CaOx ratio (Ca/Ox), which was 99.1 vs 7.5 and 67.5 vs 18.5 at T1 and T2, respectively. The high pCaOx and Ca/Ox ratios in the lactose group were due to hypercalciuria, in agreement with the number and the type of crystals. The present experimental model confirms that the ingestion of a 30% lactose diet increases urinary Ca excretion without changing urinary Ox excretion and shows for the first time that it induces a stable and marked crystalluria composed of COD. Such a non-nephrotoxic and stable model is of interest for the study of CaOx crystal formation secondary to hypercalciuria, and thus afterwards eventually for CaOx nephrolithiasis.
Animals↗
Validation by image analysis of a turbidimetric method to study calcium oxalate crystallization.
Numerous studies of calcium oxalate crystal formation have been carried out in the past two decades. In the present study, experiments were carried out to validate a turbidimetric method allowing to assess the calcium oxalate crystallization process. This method is quick and reproducible and can be used to quantify the inhibition of calcium oxalate crystal growth by various compounds. An experimental method of validation has been developed, which consisted in filtering solutions pure or containing modifiers at given crystallization times, photographing the filters used on scanning electron microscopy and analyzing the images using mathematical methodology. The results obtained through image analysis, namely crystal density (mean particle number per unit volume) and mean area, were correlated with the turbidimetric parameters. This finding was consistent with the qualitative examination of the photographs. Moreover, the morphological differences in crystals observed on the photographs were confirmed by the calculated length/width ratio. One can therefore assume that inhibition of calcium oxalate crystal growth is at least, partly explained by surface adsorption phenomena, which may add to complex formation.
Calcium Oxalate↗
Effect of erythropoietin on DNA synthesis, proto-oncogene expression and phospholipase C activity in rat vascular smooth muscle cells.
The administration of recombinant human erythropoietin (rHuEpo) to anemic chronic renal failure patients may be associated with an increase in blood pressure, possibly by direct effects on peripheral blood vessels. The experiments of the present study were designed to explore the hypothesis that rHuEpo might exert mitogenic effects on vascular smooth muscle cells (VSMCs), and that pre-existing hypertension might be a predisposing condition. Cultured aortic VSMCs from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied for DNA synthesis, phospholipase C activity, and cell growth related proto-oncogene expression in the presence of rHuEpo. In cells from both rat strains, rHuEpo dose-dependently increased DNA synthesis and stimulated phospholipase C activity, as indicated by 3H-thymidine incorporation and inositol phosphate formation, respectively. Exposure of VSMCs to rHuEpo for various periods gradually increased the levels of c-myc and JunB mRNAs and transiently induced c-fos mRNA expression as determined by Northern analysis. The hormone-induced DNA synthesis was markedly enhanced in VSMCs from SHR compared to those from WKY. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene expression did not differ between the two strains. Taken together, these results suggest that rHuEpo may function as a vascular smooth muscle cell growth promoting factor through activation of the phospholipase C cascade and a modulation of proto-oncogene expression. It could thereby contribute to vascular hypertrophy and arterial hypertension.
Animals↗
Stimulation of ileal calcium absorption by sorbitol, L-xylose, or creatine via a decrease in luminal sodium concentration: relation with concomitant changes in enterocyte energy metabolism.
Ligated ileal loops, 30 cm in length, of 4-month-old male Wistar rats were instilled with 3 ml of a 10 mM CaCl2 solution (added with 0.25 muCi 45Ca) in the absence (control) or presence of 100mM sorbitol, L-xylose, or creatine. Ileal calcium (Ca) transport, measured by plasma 45Ca appearance, was found to be similar 30 minutes after fluid instillation in all four instances. However, thereafter, 45Ca appearance in plasma did not increase further in control animals whereas it increased twice as much during the subsequent 30 minutes in the presence of sorbitol, L-xylose, or creatine. However, when loops of similar length were instilled with only 1.0 ml of such solutions, the sorbitol effect was already observed during the first 30 minutes. The stimulation of ileal Ca absorption induced by the presence of sorbitol appeared to be due to a cellular effect, associated with a decreased flux across the paracellular pathway, as indicated by 3H-mannitol absorption. The presence of sorbitol in instilled ileal solution induced a significant decrease in luminal Na, K, bicarbonate, and Cl concentrations at each time point studied (30, 60, 120, or 240 minutes after instillation). Thirty minutes after instillation, no difference in soluble Ca concentration was observed between control and experimental rats. After 60 minutes, Ca concentration was dramatically decreased in control rats but it remained nearly constant in experimental animals. Thus, the presence of substances enhancing ileal Ca transport favored the maintenance of soluble Ca in ileal solution during longer time periods than their absence. In the ileal enterocyte, these substances induced a twofold increase of ATP content compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
[In vitro effect of citrate and phosphates on calcium transport in the rat ileum].
OBJECTIVES AND METHODS: The effect of the presence of phosphates or citrate on ileal calcium (Ca) absorption was studied by using rat ileum mounted in a Ussing chamber. RESULTS: Mucosa-to-serosa and serosa-to-mucosa undirectional fluxes were not modified by mucosal addition of 2.8 mM Na phosphate or 2.0 mM Na citrate to Krebs-Ringer-bicarbonate buffer containing 1.25 mM CaCl2. However, 50 mM Na citrate induced a significant and similar increase of both unidirectional Ca fluxes, leading to no modification of net Ca flux. This high citrate concentration was associated with a significant increase of tissue conductance and no alteration of zona adherens and tight junction as observed by electron microscopy. CONCLUSIONS: Thus in the absence of any Ca gradient along the epithelium, even at high concentration, citrate did not induced modification of ileal Ca absorption.
Animals↗
A new approach to studying inhibitors of calcium oxalate crystal growth.
The nucleation and crystal growth of calcium oxalate (CaOx) were studied at pH 5.5 using turbidimetric measurements at 620 nm of suspensions produced by mixing calcium chloride and sodium oxalate (initial conditions: Ca, 3 x 10(-3) M; Ox, 0.5 x 10(-3) M). CaOx crystallization kinetics were defined first by the induction time ti and then by the slope of turbidity as a function of time during the interval corresponding to a correlation coefficient r2 > 0.99. The technique described requires only a small amount of material, is quick, convenient, and can be used to study inhibitors of CaOx crystallization by comparing ti and the rate of crystal growth in the presence and absence of inhibitors. The effects on CaOx crystal growth of several low molecular weight compounds, i.e. di- and tricarboxylic acids, were examined. The majority of these compounds were inhibitors of crystal growth, the greatest effect being seen with citric acid (50% inhibition in the presence of 1.5 x 10(-3) M citric acid), isocitric acid (50% inhibition in the presence of 0.75 x 10(-3) M isocitric acid) and pyrophosphate (30% inhibition in presence of 0.15 x 10(-3) M pyrophosphate). The inhibitors' behaviour regarding the medium was studied without any assumptions about their possible mechanisms of action. Measurements of ionized calcium before and after the reaction, as well as the observation of crystals by scanning electron microscopy, allowed us to formulate the hypothesis that the effect of citric acid and tartaric acid can be attributed mainly to ion pairing, in contrast to that of pyrophosphate and the other carboxylic acids.
Calcium↗
[Anomalies of lipoprotein metabolism in chronic renal insufficiency].
Disturbances of the lipid metabolism in chronic renal failure (CRF) are characterized by an accumulation of serum VLDL, IDL, and remnants and also by a decrease of the HDL pool, especially for HDL2. CRF is also associated with a decrease of apolipoproteins (apo) AI and AII in relation to a preferential decrease of lipoparticles (Lp) AI-AII by comparison with the anti-atherogenic Lp AI containing no AII. It is furthermore characterized by a marked increase of apo CIII, which is disproportionate with respect to the increase of apo CII and the variation of apo E, in relation with an accumulation of Lp B-CIII (and also Lp B-E and Lp B-C-E for hemodialyzed patients) in the whole spectrum of low density lipoproteins. The abnormal distribution of apo into the various classes of lipoproteins is the consequence firstly of the relative inefficacy of the lipolytic process implicated in TG-rich lipoprotein metabolism (LPL dysfunction), and secondly of the abnormal reverse cholesterol transport (anomalies of CETP and LCAT). The hormonal, nutritional, and iatrogenic factors implicated in the uremic dyslipoproteinemia are described and the implications of such abnormalities on cardiovascular disease and on the progression of renal disease are discussed.
Apolipoproteins↗
[The future of hemodialysis in the adult].
By the year 2000, the perspectives for hemodialysis performed in adults will be oriented towards facilitation of the practice of hemodialysis as a better control of clinical symptoms observed in end stage renal failure treated by hemodialysis. Blood access is the main problem which remains to be solved. The authors describe the advantages and disadvantages of the methods presently used and give the "state of the art" of "blood access" prosthesis. Almost all symptoms encountered in renal failure patients treated by hemodialysis can be efficiently treated. Hypotensive drugs usually reduce hypertension which resists adequate treatment by hemodialysis. Most of the symptoms of osteodystrophy can be avoided by adequate diet associated with the prescription of vitamin D analogs. Nevertheless, the prolongation of hemodialysis treatment duration over 7 years has led to the apparition of destructive arthropathies which are very painful and handicapping. They are related to amyloid deposit of beta 2-microglobulins. Progress in hemodialysis technics and a better control of uremic symptoms allow application of this treatment at all ages of life. The authors examine specific problems concerning school-aged teenagers and aged persons. They show that results already achieved allow a daily treatment of these patients. This is a first step for the generalisation of this procedure to all patients and its advantages are described. Improvement of hemodialysis technics for the year 2000, as can be expected, mainly depends upon progress in knowledge of biocompatibility parameters between materials used in the artificial kidney and patients tissues, mainly blood vessels.
Adult↗
Pseudotumor of the craniocervical junction during long-term hemodialysis.
A systematic study of the upper cervical spine was performed using magnetic resonance imaging in 25 patients (15 men and 10 women) who had been undergoing hemodialysis for more than 10 years. Seven pseudotumors of the periodontoid soft tissue were disclosed, which were similar to the pannus recently described in rheumatoid arthritis. Bone cystic radiolucencies were observed in association with these pseudotumors in 5 patients. The radiolucencies were located in the atlas (1 in the lateral mass and 1 in the anterior branch) and in the axis (3 in the odontoid process and 1 in the vertebral body). No horizontal or vertical atlantoaxial subluxation was demonstrated. These features were observed only in patients who had amyloid arthropathy. They could be a frequent, yet thus far little-recognized, feature of beta 2-microglobulin amyloidosis.
Adolescent↗
In vivo T cell preactivation in chronic uremic hemodialyzed and non-hemodialyzed patients.
The production and targeting of a major T cell derived lymphokine, Interleukin 2 (IL-2), were studied in 23 uremic patients undergoing regular hemodialysis treatment and 20 uremic patients prior to the onset of renal replacement therapy. In hemodialyzed patients, abnormally increased proportions of circulating T cells spontaneously expressing high affinity IL-2 receptors (IL-2 Rec) were detected: they bound a monoclonal antibody specifically directed to the IL-2 Rec 55 kDa chain (Tac antigen) (mean +/- SEM: 7.12 +/- 0.81% in patients vs. 2.15 +/- 0.39% in normal controls, P less than 0.0001) and significantly proliferated in presence of human recombinant IL-2 alone (mean +/- SEM: 5438 +/- 729 cpm in patients vs. 1647 +/- 244 cpm in normal controls). Hemodialyzed patients also exhibited significantly increased serum levels of soluble IL-2 receptor (mean +/- SEM: 4036 +/- 947 U/ml in patients vs. 253 +/- 29 U/ml in normal controls. P less than 0.001). Moreover, a significantly decreased IL-2 activity was detected in the supernatants of stimulated T cells from hemodialyzed patients (mean +/- SEM: 0.93 +/- 0.12 U/ml in patients vs. 2.49 +/- 0.22 U/ml in normal controls, P less than 0.0001). In nine hemodialyzed patients who were analyzed before and immediately after the hemodialysis session no acute modifications of the various parameters analyzed were detected. Although less profound, a similar pattern of T cell abnormalities was observed in the uremic non-hemodialyzed patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Kinetics of erythropoiesis in dialysis patients receiving recombinant erythropoietin treatment.
In eleven patients with uraemia on intermittent haemodialysis treatment, recombinant human erythropoietin (rHuEpo) was used at a dosage schedule of 100 IU/kg bodyweight thrice weekly. Erythrokinetic studies (blood volume, RBC survival and iron kinetics) were performed in nine cases before and after 6 months of treatment. The remaining two patients had only RBC and plasma volume determinations before and after treatment. Although total blood volume remained unchanged, RBC volume was increased in all cases. Red cell loss was not modified, and quantitative improvement of RBC production was noted in all cases. No qualitative defect of erythroid maturation or release was observed in the treated patients. In conclusion, rHuEpo treatment improves the anaemia of haemodialysis patients by normalising circulating RBC volume only through an increase in red cell production.
Adolescent↗
Diet-induced hyperlipoproteinemia and lipid accumulation within spontaneous arterial lesions in the rat.
The extent of diet-induced lipid accumulation evaluated histologically within rat caudal artery lesions, which represent sites of spontaneous intimal injury, was studied in relation to plasma cholesterol and lipoprotein changes in two consecutive experiments: 1) Rats were fed diets enriched with various amounts of cholesterol and saturated lipids from 5 to 12 weeks of age. A large range of values of cholesterolemia was observed at the time of sacrifice, and the more the diet was enriched in cholesterol and saturated lipids, the more the mean of the arterial score, which expressed the extent of lipid deposits within caudal artery lesions, was elevated. Among the biochemical parameters studied, in decreasing order, total cholesterol, LDLchol and VLDLchol were determinant for the arterial score. 2) Rats were fed a diet containing a moderate amount of lipids and the cholesterol concentration in the 3 classical plasma lipoprotein fractions was determined at 1.5, 3 and 6.5 weeks after starting the diet. In this experiment, statistical analysis showed that the degree of lipid accumulation within caudal artery lesions correlated only with the values of VLDLchol determined early (1.5 week) after starting the diet and not with those at the time of sacrifice. However, VLDLchol values correlated with those of LDL and total plasma cholesterol. The data from these two series of experiments suggest that in diet-induced hypercholesterolemia, the intensity of lipid deposits within areas of the arterial wall where spontaneous injury had occurred was related to the values of total plasma cholesterol as reflected both by VLDLchol and LDLchol. An independant effect of one of these lipoproteins cannot be demonstrated since they are correlated with one another.
Animals↗
Hemodialysis-associated amyloidosis and beta-2 microglobulin. Clinical and immunohistochemical study.
The beta-2 microglobulin type of amyloidosis was identified in articular and para-articular tissues of 14 patients with non-amyloid nephropathies undergoing long-term hemodialysis. Ten patients had carpal tunnel syndrome, 13 had juxta-articular radiolucent cysts (complicated by spontaneous fractures of the femoral neck in three), and six had destructive arthropathies of the large joints of the limbs. Massive amyloid deposits were found in the synovium, capsule, ligaments, articular cartilage, and/or bone. They were characterized by Congo red-induced green birefringence that was sensitive to potassium permanganate treatment. They reacted with anti-beta-2 microglobulin antiserum, whereas they did not react with antibodies directed against AA protein, prealbumin, or immunoglobulins. These data suggest that the potentially disabling arthropathy of hemodialysis is due to amyloid lesions. The persistently elevated plasma beta-2 microglobulin levels may play a role in the pathogenesis of this recently recognized complication, and if so, this complication should be preventable.
Aged↗
Synovial amyloidosis and beta 2-microglobulin in patients undergoing long-term hemodialysis.
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Amyloidosis↗
Impaired intestinal calcium transport in the spontaneously hypertensive rat.
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Animals↗